Announcement PDF ASX RELEASE 31 October 2024 Phase 3 Protocol Submission to US FDA Key Highlights • Protocol Submission: Paradigm has (PARA_OA_012) protocol to the FDA. • FDA Review: The 30-day review period with the Agency commences 29th October 2024 (Aus). • Next Steps: Following FDA review and pending no further questions from the FDA, enrolment is expected to begin in Q1 2025, starting with up to 10 Australian sites. submitted the revised Phase 3 Paradigm Biopharmaceuticals Ltd (ASX:PAR) (“Paradigm” or “the Company”), a late-stage drug development company, is pleased to announce the filing of the updated protocol for its Phase 3 clinical trial (PARA_OA_012) with the U.S. Food and Drug Administration (FDA). The 30-calendar day review period will officially begin on October 29th, upon receipt of the submission by the FDA. During this period, if the Agency does not request further information or raise additional questions, the review will conclude at the end of these 30 days. Paradigm anticipates this review to be completed within this timeframe, allowing prescreening and enrolment for the PARA_OA_012 trial to commence shortly afterward. Preparations are already underway at trial sites across Australia and the United States, with initial activities to be launched at up to 10 sites in Australia, targeting first patient enrolment by Q1 CY2025. Following FDA clearance to proceed with the Phase 3 PARA_OA_012 clinical trial, Paradigm expects to provide additional updates regarding trial design, clinical trial funding and ongoing commercial discussions. The Company is committed to keeping investors informed throughout this critical stage of the clinical program. Paul Rennie, Managing Director of Paradigm, stated: “The submission and acceptance of our Phase 3 protocol by the US FDA is a critical milestone for Paradigm, bringing us one step closer to delivering a meaningful treatment for knee osteoarthritis. We are optimistic for a smooth 30-day review period with the agency and extend our gratitude to the FDA for their valuable input throughout the Type D meeting process. Now Paradigm has made the submission of its documents to the FDA, there are two possible outcomes (i) the FDA review the protocol and have no further comments within the initial 30-day review period, which means Paradigm can commence with the Phase 3 clinical trial or (ii) the FDA has further questions within the initial 30-day review period and if so another 30 day review period will commence from the date of the Paradigm’s submitted response. The submission of the protocol along with all the associated updated clinical trial documents (see below, what has been submitted to the FDA) represents a significant achievement and reflects the hard work, persistence, dedication, and expertise of the entire Paradigm team, who have worked tirelessly to meet the stringent requirements of this program. I want to commend and thank everyone involved for their commitment to advancing our mission and for positioning us for success as we move into this pivotal phase. At Paradigm, we all have a common goal to bring Zilosul to market, and today's news is a major step forward to achieving that goal.” What has been submitted to the FDA? Making changes to a phase 3 clinical trial protocol involves a comprehensive and detailed process to ensure that any modifications align with regulatory standards and maintain the integrity of the study design. This can include adjustments to the study objectives, methodology, or patient eligibility criteria, all of which must be carefully documented and justified. For its phase 3 clinical trial (PARA_OA_012), Paradigm has submitted a protocol package comprising 12 different documents, one of which is the Investigator's Brochure (IB). This document provides clinical and preclinical information on the investigational drug, offering crucial guidance to investigators about the drug's safety profile, potential risks, and benefits. A revised Informed Consent Form (ICF) has also been provided based on recent feedback from the Agency. Each of the 12 documents a critical role in ensuring the trial adheres to FDA guidelines and safeguards participant safety, facilitating a smooth and transparent review process. -EndsAbout Paradigm Biopharmaceuticals Ltd. Paradigm Biopharmaceuticals Ltd. (ASX:PAR) is a late-stage drug development company driven by a purpose to improve patients’ health and quality of life by discovering, developing, and delivering pharmaceutical therapies. Paradigm’s current focus is developing injectable (subcutaneous) pentosan polysulfate sodium (iPPS) for the treatment of diseases where inflammation plays a major pathogenic role, indicating a need for the anti-inflammatory and tissue regenerative properties of iPPS, such as in osteoarthritis (phase 3) and mucopolysaccharidosis (phase 2). Forward Looking Statements This Company announcement contains forward-looking statements, including statements regarding anticipated commencement dates or completions dates of preclinical or clinical trials, regulatory developments and regulatory approval. These forward-looking statements are not guarantees or predictions of future performance, and involve known and unknown risks, uncertainties and other factors, many of which are beyond our control, and which may cause actual results to differ materially from those expressed in the statements contained in this presentation. Readers are cautioned not to put undue reliance on forward-looking statements. To learn more please visit: https://paradigmbiopharma.com Approved for release by the Paradigm Board of Directors. FOR FURTHER INFORMATION PLEASE CONTACT: Simon White Director of Investor Relations Tel: +61 404 216 467 Paradigm Biopharmaceuticals Ltd ABN: 94 169 346 963 Level 15, 500 Collins St, Melbourne, VIC, 3000, AUSTRALIA Email: investorrelations@paradigmbiopharma.com